Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent inherited white matter disorders in childhood,and it′s the only known hereditary human disease due to the direct defects in protein synthesis process,with the gene defects in EIF2B1-5,encoding the five subunits of eukaryotic translation initiation factor(eIF2B ?,?,?,? and ?) respectively.eIF2B is essential for the protein translation initiation process,and its action is realized via eukaryotic translation initiation factor2(eIF2).Phosphorylation of eIF2? and eIF2B? is an important way to regulate eIF2B function,and thus play a key role in control of the protein translation level under physiological condition.Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells,but in increase the translation of proteins with multiple upstream open reading frames,such as activating transcription factor 4(AFT4),which leads to the susceptibility to un-folded protein response under stress,and the following apoptosis.The exact pathogenic mechanisms of VWM are far from well understood.It′s suggested that level of AFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological condition,which makes the mutant cells more susceptible to endoplasmic reticulum(ER) stress and unfolded protein response(UPR).Under stress,the defect eIF2B leads to a vicious cycle of UPR activation,which may underlie the neurological aggravation in VWM patients after minor stress,a specific cli-nical feature of VWM.Elucidating the pathogenesis of VWM will be helpful to further understand the protein translation process in eukaryotic cells,and provide a clue for possible therapeutic targets and treatment strategies in the future.Abstract:SUMM ARY Leukoencephalopathy with vanishing white matter(VWM) is one of the most prevalent in-herited white matter d isorders in childhood,and i′ts the only known hered itary human d isease due to the d irect defects in protein synthesis process,with the gene defects inEIF2B1-5,encod ing the five sub-units of eukaryotic translation initiation factor(eIF2B?,?,?,?and?) respectively.eIF2B is essential for the protein translation initiation process,and its action is realized via eukaryotic translation initiation factor2(eIF2).Phosphorylation of eIF2?and eIF2B?is an important way to regulate eIF2B function,and thus play a key role in control of the protein translation level under physiological cond ition.Mutant eIF2B results in functional defects and decrease of the overall protein translation in cells,but in increase the translation of proteins with multiple upstream open read ing frames,such as activating transcription factor 4(AFT4),which leads to the susceptibility to un-folded protein response under stress,and the following apoptosis.The exact pathogenic mechanisms ofVWM are far from well understood.I′ts sugges-ted that level ofAFT4 in cells with eIF2B mutations is higher than in wild type cells under physiological cond ition,which makes the mutant cellsmore susceptible to endoplasm ic reticulum(ER) stress and un-folded protein response(UPR).Under stress,the defect eIF2B leads to a vicious cycle ofUPR activa-tion,which may underlie the neurological aggravation in VWM patients afterm inor stress,a specific cli-nical feature ofVWM.E lucidating the pathogenesis ofVWM will be helpful to further understand the pro-tein translation process in eukaryotic cells,and provide a clue for possible therapeutic targets and treat-ment strategies in the future.

Objective:To investigate the effects of Resina Draconis on the levels of plasma glucose,insulin and lipids in normal and diabetic rats. Methods: Hyperglycemia rat models were induced by glucose or adrenaline and rat models with diabetes mellitus were induced by alloxan.The levels of plasma glucose, insulin and lipids (triglyceride, total cholesterol and HDL-C) were determined. Results: Resina Draconis had no obvious effects in decreasing the plasma sugar level in normal fasted rats but could decrease the plasma sugar level and improve the glucose-resistance in glucose-induced or adrenaline-induced hyperglycemic rats and alloxan-induced fasted diabetic rats and increase insulin secretion in both normal and diabetic rats. It could also decrease the plasma lipid level in alloxan-induced diabetic rats. Conclusion: Resina Draconise exerts a good therapeutic effect on hyperglycemia in diabetic rats and its mechanism may be related to the increase of the secretion of insulin.

OBJECTIVE:To investigate the use and its developing trend of antidiabetics in our hospital.METHODS:A statistical analysis was conducted on the consumption sum,DDDs of antidiabetics used in our hospital from 2002 to 2006.RESULTS:Over the 5 years,the average annual incremental rates of oral antidiabetics in consumption sum,DDDs were 38.94% and 22.56%,respectively,with the kinds from joint venture and home showing the highest increasing range in consumption sum and DDDs,respectively.CONCLUSION:Antidiabetics used in our hospital has confirmed efficacy,and the kinds from home assume a predominant place,therefore,research and development for domestic drugs should be strengthened.

Objective To observe the incidence of critical illness-related corticosteroid insufficiency (CIRCI) after severe traumatic brain injury (sTBI) and investigate the relationship between CIRCI and prognosis.Methods This prospective cohort study enrolled 89 sTBI patients (68 males and 21 females;at age range of 15-80 years) hospitalized within 24 hours after sTBI from June 2014 to December 2015.The Glasgow coma scale (GCS) was ≤8 points.The causes of injury included extensive contusion of brain (44 cases),subdural hematoma (21 cases),epidural hematoma (11 cases),primary brain stem injury (8 cases) and diffuse axonal injury (5 cases).Adrenocorticotropic hormone (ACTH) stimulation tests were done within 36 hours after sTBI to identify CIRCI patients.The patients were divided into CIRCI group (50 cases) and non-CIRCI group (39 cases).Moreover,the patients were categorized into survival group (62 cases) and death group (27 cases) based on survival status.The GCS score,mechanical ventilation time,cerebral hernia,survival time and mortality within 28 days were observed in two groups.Results The incidence of CIRCI in sTBI patients was as high as 56％ (50/89).Compared with the non-CIRCI group,the CIRCI group had lower GCS [(5.3 ± 1.7) points vs.(6.1 ± 1.4) points,P ＜ 0.05],and sTBI patients with CIRCI were mechanically ventilated for a longer period of time [(9.9 ± 2.8) days vs.(7.5 ± 1.6) days,P ＜ 0.05].In comparison with non-CIRCI patients,the incidence of brain herniation in sTBI patients with CIRCI was higher (58％ vs.21％,P ＜0.01).The total fatality rate within 28 days was 30％ (27/89).The survival time of CIRCI group was significantly shorter than that of non-CIRCI group (P ＜ 0.05).The fatality rate in the CIRCI group was significantly higher than that of the non-CIRCI group [40％ (20/50) vs.18％ (7/39),P ＜0.05].The incidence of CIRCI in death group was significantly higher than that of the survival group [74％ (20/27) vs.48％ (30/62),P ＜ 0.05].Conclusions The incidence of CIRCI in STBI patients is high.The sTBI patients with CIRCI has significantly higher incidence of brain hernia,longer mechanical ventilation time,higher 28-day mortality and shorter survival time compared with non-CIRCI patients.

Aim To investigate the effect of MTX(included(±)MTX,(+)MTX and(-)MTX)on the proliferation of ECV304 cells and to explore its mechanisms.Methods ECV304 cells were cultured.The cell proliferation was determined by MTT.The morphological changes were inspected by inverted microscope.Cell cycle phases were assayed by propidium iodide staining flow cytometry.Results ECV304 cells were treated with(+)MTX,(-)MTX and(±)MTX at 1～150 μmol·L~(-1) for 24,48,72 h.The results showed that the proliferation of ECV304 cells was significantly inhibited under different conditions.The order of the inhibited efficacy was(+)MTX>(±)MTX>(-)MTX.The morphology of ECV304 cells were changed by(+)MTX,(-)MTX and(±)MTX treatment,which included the cell shrinkage,chromatin condensation.After administration of 10 μmol·L~(-1) of(+)MTX,(-)MTX and(±)MTX for 48 h,the cell cycle phases were assayed by propidium iodide staining flow cytometry.The result showed DNA replication was interfered by(+)MTX,(-)MTX and(±)MTX treatment.Conclusions The proliferation of ECV304 cells has the chiral selective effects by(+)MTX and(-)MTX treatment,and the inhibition on ECV304 cells proliferation of(+)MTX is significantly stronger than that of (-)MTX.

The paper is to report the pharmacokinetics of furosemide in rats living at plain area and high altitude. After intragastric administration of furosemide (2.87 mg x kg(-1)), serial blood samples (0.5 mL) were collected by retro-orbital puncture at 0, 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h, samples were determined by LC-MS/MS, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters. The main pharmacokinetic parameters: area under curve (AUC), mean residence time (MRT), the biological half-life (t1/2) and the peak concentration (C(max)) of furosemide, were significantly increased at high altitude, the time to reach peak concentration (t(max)) and clearance (CL) was significantly decreased. This study found significant changes on the pharmacokinetics of furosemide under the special environment of high altitude. This finding may provide some references for clinical rational application of furosemide at high altitude.

ObjectiveTo investigate the accuracy of automated breast volume scanning (ABVS) for the measurement of breast tumor size.MethodsSixty-two breast tumors in 59 patients were included in this study and were examined using conventional ultrasound and ABVS to measure the maximal diameters of the tumors. And the measurement results were compared with the pathological maximal diameters.Results There were 21 malignant and 41 benign tumors according to histopathological evaluation. There were no signifi cant differences between the maximal diameters on ABVS and on pathological measurements for both benign tumors and malignant tumors (Z=1.761, 0.262,P=0.078, 0.794). However, for malignant tumors, the maximal diameters on conventional ultrasound were significantly smaller than those on pathological measurements (Z=3.743,P=0.000). For benign tumors, the maximal diameters on conventional ultrasound were similar with those on pathological measurements (Z=1.935,P=0.053). The measurement values of conventional ultrasound and ABVS were both positively correlated with those on pathological values (r=0.935, 0.964,r=0.870, 0.964). And the correlation coeffi cients between ABVS and pathological measurement values were higher than those between conventional ultrasound and pathological measurement values for both benign and malignant tumors. ConclusionABVS can assess the size of breast tumor more accurately than conventional ultrasound, especially for the malignant tumors.

Objective To explore the influence of lower concentration of cell free fetal fraction DNA in maternal plasma on non-invasive prenatal test(NIPT) .Methods A total of 3240 pregnant women accepted NIPT in Foshan Maternal and Children′s Hos-pital from April ,2015 to March ,2016 were analyzed retrospectively ,and 150 samples of which were male fetus judged by Z score of Y chromosome and the cell free fetal fraction DNA were lower than 8% were selected .The cell free fetal fraction DNA were in-creased by agarose gel electrophoresis ,then conducted NIPT ,compared with the results of aneuploidy screening .Results The cell free fetal fraction DNA were increased from 5% to 9 .2% by agarose gel electrophoresis .The result of NIPT after increasing fetal fraction was consistent with it before .Conclusion Concentration of cell free fetal fraction DNA has no influence on the result of NIPT when cell free fetal fraction DNA is above 5% .

Objective To investigate the protective effect and its mechanism of infradiaphragmatic stasis-expelling decoction on hepatic fibrosis in rats. Method One hundred and ten SD rats were divided into four groups:the normal control group ,model group ,low dose group and high dose group of infradiaphragmatic stasis-expelling decoction. In addition to the normal control group,rats in other groups were subcutaneously given pure CCl4 to set up the liver fibrosis model. Twelve weeks later,the serum liver biochemical indexes,including ALT,AST, ALB,TP and T-bil,the Ishak score about liver fibrosis ,the positive expression of TIMP-1 were compared among groups. Results Compared with the fibrotic group,the levels of serum ALT,AST and T-bil were lower in low dose group,the level of serum TP and ALB were increased in high dose group Levels of serum ALT,AST and T-bil were significantly lowered in high dose group,the levels of serum of TP and ALB were significantly increased in high dose group. Compared with model group,the Ishak score about liver fibrosis was significantly lowered(P<0.05). Numbers of cells with positive expression of TIMP-1 in liver tissue was reduced. Conclusion Infradiaphragmatic stasis-expelling decoction could inhibit the expression and activity of TIMP-1 contributing to the effect of antiliver fibrosis.

To summarize the advances in mechanisms of damage and treatments of cerebral ischemia and reperfusion and fore -casts future research directions .The existing achievements in literatures were summarized .Cerebral ischemia and reperfusion damage were related to inflammatory response , intracellular calcium overload , free radicals injury , release of excitatory amino acids and other factors.The treatments included reducing ischemia time , blocking glutamate receptors , free radical scavenging , inhibition of apoptosis , reducing inflammation , and promoting neuronal growth , etc.Multi-target treatment would be future directions in treatment of cerebral ischemia.